Ascidians (tunicates) contain compounds with a large range of pharmacological activities. With the most[unreadable] common of chemical ingredients, elemental sulfur and dopamine, an ascidian has developed a means to[unreadable] protect itself from predators using in essence chemical warfare. With lessons that marine organisms can[unreadable] provide, how might chemists seek the advent of new therapeutic substances from abundant and simple[unreadable] natural reagents? The problem is that we lack an understanding of the biosynthetic pathways that marine[unreadable] organisms use to make protective or otherwise purposeful molecules from benign common precursors. A[unreadable] long-term objective of this program is to synthesize sulfur?dopamine compounds that may have enhanced[unreadable] biological activity compared to what nature provides. This proposal outlines an experimental and theoretical[unreadable] organic chemistry approach to addressing the structure and synthesis of polysulfane antitumor compounds.[unreadable] Mechanistic information will be sought in reactions that mimic a biosynthetic process to help in designing[unreadable] new drugs. The goals of the research project are: (1) to examine the chemical mechanism for the formation[unreadable] of natural product antitumor polysulfanes formed from dopamine, and determine the product yields and[unreadable] product reaction profiles, (2) to identify the chemical form of sulfur that can add to dopamine and related[unreadable] natural aromatics such as catechol, (3) to define certain steps in the mechanism of formation of the[unreadable] polysulfur linkage, (4) to determine whether observed trends in heterocycle odd-even membered ring effects[unreadable] serve as a guide in the synthesis of pharmaceutically active polysulfane molecules, (5) to synthesize[unreadable] sulfur?dopamine compounds that have enhanced biological activity compared to what nature provides, and[unreadable] (6) to establish a collaborative research program such that the molecules produced in our laboratory will be[unreadable] examined as possible lead compounds, which may eventually be used clinically as antitumor and antibiotic[unreadable] agents. Research design and methods will involve experiments that utilize HPLC, GC/MS, NMR, and kinetic[unreadable] analyses for characterizations of the mechanisms. Theoretical calculations will be performed to discover the[unreadable] factors that are likely to influence polysulfane synthesis and decomposition with the aim of evaluating the[unreadable] viability of the intermediates.